Graphene displays properties that make it appealing for neuroregenerative medicine, yet its interaction with peripheral neurons has been scarcely investigated. Here, we culture on graphene two established models for peripheral neurons: PC12 cells and DRG primary neurons. We perform a nano-resolved analysis of polymeric coatings on graphene and combine optical microscopy and viability assays to assess the material cytocompatibility and influence on differentiation. We find that differentiated PC12 cells display a remarkably increased neurite length on graphene (up to 27%) with respect to controls. Notably, DRG primary neurons survive both on bare and coated graphene. They present dense axonal networks on coated graphene, while they form cell islets characterized by dense axonal bundles on uncoated graphene. These findings indicate that graphene holds potential for nerve tissue regeneration and might pave the road to novel concepts of active nerve conduits.

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Peripheral Neuron Survival and Outgrowth on Graphene

The pinned photodiode is the primary photodetector structure used in most CCD and CMOS image sensors. This paper reviews the development, physics, and technology of the pinned photodiode.

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A Review of the Pinned Photodiode for CCD and CMOS Image Sensors

This paper investigates terahertz detectors fabricated in a low-cost 130 nm silicon CMOS technology. We show that the detectors consisting of a nMOS field effect transistor as rectifying element and an integrated bow-tie coupling antenna achieve a record responsivity above 5 kV/W and a noise equivalent power below 10 pW/Hz(0.5) in the important atmospheric window around 300 GHz and at room temperature. We demonstrate furthermore that the same detectors are efficient for imaging in a very wide frequency range from ~0.27 THz up to 1.05 THz. These results pave the way towards high sensitivity focal plane arrays in silicon for terahertz imaging.

Broadband terahertz imaging with highly sensitive silicon CMOS detectors

Single-photon avalanche diode (SPAD) arrays are solid-state detectors that offer imaging capabilities at the level of individual photons, with unparalleled photon counting and time-resolved performance. This fascinating technology has progressed at a very fast pace in the past 15 years, since its inception in standard CMOS technology in 2003. A host of architectures have been investigated, ranging from simpler implementations, based solely on off-chip data processing, to progressively "smarter" sensors including on-chip, or even pixel level, time-stamping and processing capabilities. As the technology has matured, a range of biophotonics applications have been explored, including (endoscopic) FLIM, (multibeam multiphoton) FLIM-FRET, SPIM-FCS, super-resolution microscopy, time-resolved Raman spectroscopy, NIROT and PET. We will review some representative sensors and their corresponding applications, including the most relevant challenges faced by chip designers and end-users. Finally, we will provide an outlook on the future of this fascinating technology.

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Single-photon avalanche diode imagers in biophotonics: review and outlook

We introduce a 512 × 424 time-of-flight (TOF) depth image sensor designed in a TSMC 0.13 μm LP 1P5M CMOS process, suitable for use in Microsoft Kinect for XBOX ONE. The 10 μm × 10 μm pixel incorporates a TOF detector that operates using the quantum efficiency modulation (QEM) technique at high modulation frequencies of up to 130 MHz, achieves a modulation contrast of 67% at 50 MHz and a responsivity of 0.14 A/W at 860 nm. The TOF sensor includes a 2 GS/s 10 bit signal path, which is used for the high ADC bandwidth requirements of the system that requires many ADC conversions per frame. The chip also comprises a clock generation circuit featuring a programmable phase and frequency clock generator with 312.5-ps phase step resolution derived from a 1.6 GHz oscillator. An integrated shutter engine and a programmable digital micro-sequencer allows an extremely flexible multi-gain/multi-shutter and multi-frequency/multi-phase operation. All chip data is transferred using two 4-lane MIPI D-PHY interfaces with a total of 8 Gb/s input/output bandwidth. The reported experimental results demonstrate a wide depth range of operation (0.8–4.2 m), small accuracy error ( $ 1%), very low depth uncertainty ( $ 0.5% of actual distance), and very high dynamic range ( $>$ 64 dB).

A 0.13 μm CMOS System-on-Chip for a 512 × 424 Time-of-Flight Image Sensor With Multi-Frequency Photo-Demodulation up to 130 MHz and 2 GS/s ADC

Light detection and ranging (LiDAR) systems are enabling new applications in the field of spacecraft navigation, planetary exploration, as well as docking and landing operations. Wide time-of-flight (ToF) range, high speed and spatial resolution, tolerance to background (BG) noise, high dynamic range and radiation hardness represent some of key features to operate in this harsh environment. Among all technologies, direct ToF sensors based on CMOS single-photon avalanche diodes (SPAD) and time-to-digital converter (TDC) pixel arrays have gradually earned their place in 3D imaging due to their performance and system integrability [1]–[4].

A $64\times 64$-Pixel Flash LiDAR SPAD Imager with Distributed Pixel-to-Pixel Correlation for Background Rejection, Tunable Automatic Pixel Sensitivity and First-Last Event Detection Strategies for Space Applications

A low-cost integrated microsensor for biomedical applications is proposed. It is composed by an antenna-coupled microbolometer as detector, which is coupled to a specifically designed integrated circuit for biasing and readout. The main features are fast response to radiation, device level reference sensor, and electronic time-correlation for pulsed sources. The detector and the integrated circuits have been fabricated in a custom MEMS technology and a standard CMOS technology, respectively. First electrical measurements show properly operating devices.

Terahertz microsensor for biomedical applications

In this article a comprehensive modeling of cold-biased field-effect transistors (FETs) used as terahertz (THz) detectors is developed. The described model is based upon the transistor Enz-Krummenacher-Vittoz (EKV) model in order to provide valid quantities also near and below the transistor threshold by using available technology parameters, without any extra fitting nor calibration. Important aspects such as the antenna coupling and the effect of amplitude modulation of the THz source are considered in a single, handy, analytical model. THz measurements performed on specifically designed FET detectors confirm its validity, providing a powerful tool and giving a clear insight of the role of available variables. The model can anticipate time-consuming numerical simulations or more physically accurate models requiring experimental parameters calibration, that may complement the results for better accuracy.

A Compact Current- and Voltage-Mode Model of Antenna-Coupled FET Terahertz Detectors

A low-noise readout interface integrated with an antenna-coupled FET-based terahertz (THz) detector is designed and fabricated in a 0.15-μm CMOS standard technology. The implemented readout includes a cascade of a preamplification noise reduction stage based on a parametric chopper amplifier, and a direct analog-to-digital conversion by means of an incremental ΣΔ converter, substituting the lock-in apparatus. The measured input referred noise of 1.6 μVrms allows preserving the FET detector noise performance. The characterization results show that the noise equivalent power (NEP) of the THz detector and readout chain is of 376 pW/√Hz at the optimal bias point while providing directly a digital output. The integrated readout chain features 65 dB maximum SNR and occupies an area of 90 × 300 μm2, with 80 μW power consumption from 1.8 V supply.

A noise-efficient, in-pixel readout for FET-based THz detectors with direct incremental A/D conversion

In quantum imaging techniques, entangled photons are used to overcome the limits of classical-light apparatus, in terms of image quality (beating the standard shot-noise limit) and resolution (exceeding the Abbe diffraction limit).1–3 In modern quantum imaging experiments, however, the spatial properties of the entangled photons are recorded by means of complex and slow setups.4 That is, the systems either involve motorized scanning of single-pixel single-photon detectors—such as photomultiplier tubes (PMTs) or silicon photomultipliers (SiPMs)—or the use of low-frame-rate-intensified CCD cameras. To enable further developments of quantum imaging techniques, simpler entangledphoton detection systems (with faster acquistion times) are thus required. Arrays of single-photon avalanche diodes (SPADs) implemented in standard CMOS technology are a relatively recent development in the field of single-photon detection. This technology provides a timing performance similar to that of PMTs and SiPMs at a high spatial resolution.5 To date, CMOS SPAD technology has found applications in biology (for fluorescence lifetime imaging microscopy6 and Raman spectroscopy7), in medicine (for positron emission tomography8), in the automotive and space industries (for 3D time-of-flight measurements9–11), as well as in cryptography (for quantum random number generation12). In addition, CMOS SPAD consumer products have recently become commercially available as light detection and ranging devices (for smartphone camera autofocusing).13 In our work,14 we are also looking to develop a new generation of optical microscope systems (by exploiting the properties of entangled photons to acquire images at a resolution beyond the classical Rayleigh limit). As part of our All Solid-State Super-Twinning Photon Microscope (SUPERTWIN) Figure 1. (a) Micrograph of the SPADnet-I chip (SPAD: single-photon avalanche diode). Inset shows a close-up on a single pixel of the chip, which includes 720 SPADs and (in the middle) the electronics required for calibration, SPAD operation, photon counting, and photon timestampling. I/O: Input/output. (b) Illustration of the SPADnet-I acquisition timing during a quantum physics experiment. The chip records a timestamp per pixel in two consecutive clock bins. The data is then read out in less than 4 s, with the clock running at a frequency of 100MHz. The scheme is shown here for two separate pixels, i.e., (i,j) and (k,l). t: Time.

Matteo Perenzoni

Papers

A $64\times 64$-Pixel Flash LiDAR SPAD Imager with Distributed Pixel-to-Pixel Correlation for Background Rejection, Tunable Automatic Pixel Sensitivity and First-Last Event Detection Strategies for Space Applications

Terahertz microsensor for biomedical applications

A Compact Current- and Voltage-Mode Model of Antenna-Coupled FET Terahertz Detectors

A noise-efficient, in-pixel readout for FET-based THz detectors with direct incremental A/D conversion

Novel CMOS sensors for improved quantum imaging